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ERG (ETS-related gene) is a proto-oncogene, a member of the ETS family of transcription factors. The ERG gene encodes for a nuclear protein, also called ERG, which is involved in hematopoietic and endothelial development. ERG remains constitually expressed in endothelial cells in blood and lymphatic vessels, and in bone marrow stem cells. ERG is expressed in virtually all endothelial neoplasms including hemangioendothelioma, angiosarcoma and Kaposi sarcoma. ERG is overexpressed secondary to gene rearrangement in cases of prostate adenocarcinoma, gastrointestinal stromal tumor, synovial sarcoma, meningioma, epithelioid sarcoma, malignant rhabdoid tumor, acute myeloid leukemia and blastic extramedullary myeloid tumor, and rarely Ewing sarcoma / primitive peripheral neuroectodermal tumor, chondrosarcoma, osteosarcoma, and rhabdomyosarcoma. For the identification of endothelial differentiation ERG seems more sensitive and specific than any other marker. Moreover, the interpretation is often easier due to the nuclear reaction, which also allows for double stains with cytoplasmic markers like podoplanin. Among carcinomas, ERG is highly specific for prostate, while the sensitivity is moderate.
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